Development of a<i>Chlamydia trachomatis</i>bacterial ghost vaccine to fight human blindness

Eko, Francis O.; Barisani-Asenbauer, Talin; Lubitz, Werner

doi:10.4161/hv.4.3.5393

Cited by 18 publications

(9 citation statements)

References 57 publications

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“…Bacterial Ghosts (BGs) represent empty bacterial cell envelopes of Gram-negative bacteria developed as a novel carrier for DNA, Ags, enzymes, drugs, and adjuvant system for the delivery of mucosal (Eko et al, 2008;Kudela et al, 2010;Tabrizi et al, 2004). BGs are produced by protein E-mediated lysis of Gram-negative bacteria.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Ghosts as antigen and drug delivery system for ocular surface diseases: Effective internalization of Bacterial Ghosts by human conjunctival epithelial cells

Kudela¹,

Koller²,

Mayr³

et al. 2011

Journal of Biotechnology

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Section: Introductionmentioning

confidence: 99%

Bacterial Ghosts as antigen and drug delivery system for ocular surface diseases: Effective internalization of Bacterial Ghosts by human conjunctival epithelial cells

Kudela¹,

Koller²,

Mayr³

et al. 2011

Journal of Biotechnology

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“…Bacterial ghosts (BGs) represent empty bacterial cell envelopes of Gram‐negative bacteria developed as a novel carrier for DNA, antigen (Ag), enzymes, drugs and adjuvant system for the delivery of mucosal vaccines (Tabrizi et al ., 2004; Eko et al ., 2008; Lubitz et al ., 2009; Kudela et al ., 2010). Bacterial ghosts are produced by controlled expression of the cloned φX174 gene E , which results in protein E‐mediated lysis of Gram‐negative bacteria and the formation of empty bacterial cell envelopes with surface and structural components in a natural non‐denatured form (Witte et al ., 1992; Szostak et al ., 1996; Eko et al ., 1999).…”

Section: Introductionmentioning

confidence: 99%

Rectal single dose immunization of mice with Escherichia coli O157:H7 bacterial ghosts induces efficient humoral and cellular immune responses and protects against the lethal heterologous challenge

Mayr¹,

Kudela²,

Atrasheuskaya

et al. 2011

Microbial Biotechnology

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SummaryBacterial ghosts (BGs) have been applied through oral, aerogenic, intraocular or intranasal routes for mucosal immunization using a wide range of experimental animals. All these applications required a booster after primary immunization to achieve protective immunity against the lethal challenge. Here we report for the first time that a single rectal dose of BGs produced from enterohaemorrhagic Escherichia coli (EHEC) O157:H7 fully protects mice against a 50% lethal challenge with a heterologous EHEC strain given at day 55. BGs from EHEC O157:H7 were prepared by a combination of protein E‐mediated cell lysis and expression of staphylococcal nuclease A guaranteeing the complete degradation of pathogen residual DNA. The lack of genetic material in the EHEC BGs vaccine abolished any potential hazard for horizontal gene transfer of plasmid encoded antibiotic resistance genes or pathogenic islands to the recipient's gut flora. Single rectal immunization using EHEC O157:H7 BGs without any addition of adjuvant significantly stimulated efficient humoral and cellular immune responses, and was equally protective as two immunizations, which indicates the possibility to develop a novel efficacious single dose mucosal EHEC O157:H7 BGs vaccine using a simplified immunization regimen.

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“… 5 , 31 BGs are straightforward to produce, cost-effective and require no special storage conditions aside from freeze-drying to maintain their potency for years. 5 , 7 , 14 The probiotic EcN BG would form an easy-to-produce GMP compatible delivery system with innate immune system-recognized surface structures with intrinsic immunomodulatory effects. 16 Lacking any ability to infect or colonize, EcN BGs form an elegant and safe method of drug or antigen delivery to the ocular mucosal surface.…”

Section: Discussionmentioning

confidence: 99%

“…These beneficial immunomodulatory effects 11 – 13 could contribute to the prevention of ocular surface diseases. 5 , 14 …”

Section: Introductionmentioning

confidence: 99%

Escherichia coli Nissle 1917 bacterial ghosts retain crucial surface properties and express chlamydial antigen: an imaging study of a delivery system for the ocular surface

Montanaro

Inić-Kanada

Ladurner

et al. 2015

DDDT

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To target chronic inflammatory ocular surface diseases, a drug delivery platform is needed that is safe, possesses immunomodulatory properties, and can be used either for drug delivery, or as a foreign antigen carrier. A new therapeutic approach that we have previously proposed uses nonliving bacterial ghosts (BGs) as a carrier-delivery system which can be engineered to carry foreign antigens and/or be loaded with therapeutic drugs. The parent strain chosen for development of our BG delivery system is the probiotic Escherichia coli strain Nissle 1917 (EcN), whose intrinsic properties trigger the innate immune system with the flagella and fimbriae used to attach and stimulate epithelial cells. In previous studies, we have shown that EcN BGs are safe for the ocular surface route, but evidence that EcN BGs retain flagella and fimbriae after transformation, has never been visually confirmed. In this study, we used different visualization techniques to determine whether flagella and fimbriae are retained on EcN BGs engineered either for drug delivery or as a foreign antigen carrier. We have also shown by immunoelectron microscopy that EcN retains two foreign antigens after processing to become EcN BGs. Furthermore, we demonstrated that BGs derived from EcN and expressing a foreign antigen attachment to conjunctival epithelial cells in vitro without causing reduced cell viability. These results are an important step in constructing a delivery system based on a nonliving probiotic that is suitable for use in ocular surface diseases pairing immunomodulation and targeted delivery.

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Development of aChlamydia trachomatisbacterial ghost vaccine to fight human blindness

Cited by 18 publications

References 57 publications

Bacterial Ghosts as antigen and drug delivery system for ocular surface diseases: Effective internalization of Bacterial Ghosts by human conjunctival epithelial cells

Bacterial Ghosts as antigen and drug delivery system for ocular surface diseases: Effective internalization of Bacterial Ghosts by human conjunctival epithelial cells

Rectal single dose immunization of mice with Escherichia coli O157:H7 bacterial ghosts induces efficient humoral and cellular immune responses and protects against the lethal heterologous challenge

Escherichia coli Nissle 1917 bacterial ghosts retain crucial surface properties and express chlamydial antigen: an imaging study of a delivery system for the ocular surface

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